Summary of the ESC/EACTS 2014 Guidelines on myocardial ... · Guidelines Summary of the ESC/EACTS 2014 Guidelines on myocardial revascularization. Prepared by the Czech Society of

Guidelines

Summary of the ESC/EACTS 2014 Guidelines onmyocardial revascularization. Prepared by theCzech Society of Cardiology§

Petr Kala a,*, Michael Zelizko b, Jan Pirk b

aClinic of Internal Medicine – Cardiology, Medical Faculty of Masaryk University and University Hospital Brno, Brno,Czech Republicb Institute of Clinical and Experimental Cardiology, Prague, Czech Republic

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2

a r t i c l e i n f o

Article history:

Received 6 April 2015

Received in revised form

18 May 2015

Accepted 19 May 2015

Available online 17 June 2015

§ For permissions: please e-mail: [email protected].* Corresponding author at : Medical Faculty of Masaryk University and University Hospital Brno, Jihlavska 20, 625 00 Brno, Czech Republic.

Tel.: +420 532232205; fax: +420 532232161.E-mail address: [email protected] (P. Kala).Abbreviations: ACCF/AHA, American College of Cardiology Foundation/American Heart Association; ACS, acute coronary syndromes; AF,

atrial fibrillation; ASA, acetylsalicylic acid; BMS, bare-metal stent; CABG, coronary artery bypass grafting; CAD, coronary artery disease;CARDIA, Coronary Artery Revascularization in Diabetes; CAS, carotid artery stenting; CCS, Canadian Cardiovascular Society; CEA, carotidendarterectomy; CKD, chronic kidney disease; COURAGE, Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation;CTO, chronic total occlusion; CURRENT-OASIS 7, Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events – SeventhOrganization to Assess Strategies in Ischemic Syndromes 7; DES, drug-eluting stent; DTB, door-to-balloon time; EACTS, European Associationfor Cardio-Thoracic Surgery; EAPCI, European Association of Percutaneous Cardiovascular Interventions; ESC, European Society of Cardiolo-gy; FAME, Fractional Flow Reserve vs. Angiography for Multivessel Evaluation; FFR, fractional flow reserve; FINESSE, Facilitated Interventionwith Enhanced Reperfusion Speed to Stop Events; FREEDOM, Future Revascularization Evaluation in Patients with Diabetes Mellitus; GFR,glomerular filtration rate; GPI/IIb/IIIa, glycoprotein IIb/IIIa inhibitors; HR, hazard ratio; IABP, intra-aortic balloon pump; IABP-SHOCK, Intra-aortic Balloon Pump in Cardiogenic Shock; ICD, implantable cardioverter defibrillator; IMA, internal mammary artery; INR, internationalnormalized ratio; IVUS, intravascular ultrasound imaging; LAA, left atrial appendage; LAD, left anterior descending; LM, left main; LMWH,low-molecular-weight heparin; LoE, level of evidence; LV, left ventricle/left ventricular; LVEF, left ventricular ejection fraction; MACCE, majoradverse cardiac and cerebrovascular event; MACE, major adverse cardiac event; MI, myocardial infarction; NOAC, non-vitamin K antagonistoral anticoagulant; NSTE-ACS, non-ST-segment elevation acute coronary syndrome; On-TIME-2, Continuing TIrofiban in Myocardialinfarction Evaluation; OR, odds ratio; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; PLATO, Study of PlateletInhibition and Patient Outcomes; PRAMI, Preventive Angioplasty in Acute Myocardial Infarction; PRECOMBAT, Premier of RandomizedComparison of; RCT, randomized clinical trial; RRR, relative risk reduction; SCAD, stable coronary artery disease; SHOCK, Should WeEmergently Revascularize Occluded Coronaries for Cardiogenic Shock; STEMI, ST-segment elevation myocardial infarction; STICH, SurgicalTreatment for Ischemic Heart Failure; SVG, saphenous vein graft; SVR, surgical ventricular reconstruction; SYNTAX, Synergy betweenPercutaneous Coronary Intervention with TAXUS and Cardiac Surgery; TAVI, transcatheter aortic valve implantation; TIA, transientischaemic attack; TIMACS, Timing of Intervention in Patients with Acute Coronary Syndromes; TIMI, Thrombolysis in Myocardial Infarction;TRITON TIMI-38, TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel–Thrombolysis InMyocardial Infarction 38; TVR, target vessel revascularization; UFH, unfractionated heparin; VD, vessel disease.

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Contents

1. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3842. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3843. Scores and risk stratification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3844. Process for decision-making and patient information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e384

4.1. Patient information and informed consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3844.2. Multidisciplinary decision-making (Heart Team) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3844.3. Timing of revascularization and ad hoc PCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e385

5. Strategies for diagnosis: functional testing and imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3855.1. Non-invasive tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3855.2. Invasive tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3855.3. Detection of myocardial viability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e385

6. Revascularization for stable coronary artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3856.1. Revascularization with the use of PCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3856.2. PCI with DES vs. BMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3856.3. Revascularization with the use of CABG (Table 6). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3866.4. PCI vs. CABG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e386

7. Revascularization in non-ST-segment elevation acute coronary syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3877.1. Early invasive vs. conservative strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3877.2. Timing of angiography and intervention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3877.3. Type of revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e387

7.3.1. CABG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3887.3.2. PCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e388

8. Revascularization in ST-segment elevation myocardial infarction (Fig. 1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3888.1. PCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3888.2. Fibrinolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3898.3. CABG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e389

9. Revascularization in patients with heart failure and cardiogenic shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3909.1. Chronic heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e3909.2. Cardiogenic shock. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e390

10. Revascularization in patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39110.1. Evidence for myocardial revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e391

10.1.1. Stable coronary artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39110.1.2. Acute coronary syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e391

10.2. Type of myocardial revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e391

Authors of the original ESC/EACTSdocument [1]: Stephan Windecker,Philippe Kolh on behalf of the TaskForce on Myocardial Revascularizationof the European Society of Cardiology(ESC) and the European Association forCardio-Thoracic Surgery (EACTS)Developed with the special contributionof the European Association ofPercutaneous CardiovascularInterventions (EAPCI).

Keywords:

Acute coronary syndromes

Bare-metal stents

Coronary artery bypass grafting

Coronary artery disease

Drug-eluting stents

Guidelines

Heart Team

Myocardial infarction and ischaemia

Myocardial revascularization

Percutaneous coronary intervention

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2e382

10.3. Revascularization with the use of PCI or CABG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39210.4. Antithrombotic and anti-diabetic medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e392

11. Revascularization in patients with chronic kidney disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39212. Revascularization in patients requiring valve interventions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e392

12.1. Primary indication for valve interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39212.2. Primary indication for coronary revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e392

13. Associated carotid/peripheral artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39213.1. Associated coronary and carotid artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39213.2. Associated coronary and peripheral arterial disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e393

14. Repeat revascularization and hybrid procedures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39315. Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e394

15.1. Ventricular arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39415.2. Atrial arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39515.3. Concomitant surgical procedures for atrial fibrillation or stroke treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . e395

16. Procedural aspects of coronary artery bypass grafting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1. Surgical procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e395

16.1.1. Conduit harvest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.2. Coronary vessel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.3. Completeness of revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.4. Construction of central anastomosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.5. Bypass grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.6. On-pump and off-pump procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39516.1.7. Minimally invasive procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e395

16.2. Reporting perioperative outcome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39517. Procedural aspects of percutaneous coronary intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e395

17.1. Percutaneous coronary intervention devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39517.2. Adjunctive invasive diagnostic tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39517.3. Specific lesion subsets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e396

18. Antithrombotic treatments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39618.1. Percutaneous coronary intervention in stable coronary artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e396

18.1.1. Oral antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39618.1.2. Intravenous antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39618.1.3. Anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e396

18.2. Non-ST-segment elevation acute coronary syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39718.2.1. Oral antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39718.2.2. Intravenous antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39718.2.3. Anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e397

18.3. ST-segment elevation myocardial infarction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39718.3.1. Oral antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39718.3.2. Intravenous antiplatelet therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39818.3.3. Anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e398

18.4. Points of interest and special conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39818.4.1. Pre-treatment with P2Y12 inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39818.4.2. Intravenous P2Y12 inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39818.4.3. Anticoagulation after percutaneous coronary intervention in acute coronary syndrome patients . . . e39818.4.4. Anticoagulation during percutaneous coronary intervention in patients on oral anticoagulation . . . e39818.4.5. Antithrombotic therapy after percutaneous coronary intervention in patients requiring oral anticoagula-

tion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e39818.4.6. Duration of dual antiplatelet therapy after percutaneous coronary intervention. . . . . . . . . . . . . . . . . e40018.4.7. Drug interactions: a clopidogrel-related topic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40018.4.8. Renal dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40018.4.9. Surgery in patients on dual antiplatelet therapy (Fig. 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40018.4.10. Antiplatelet therapy monitoring and genetic testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40018.4.11. Patients with hypersensitivity to acetylsalicylic acid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40018.4.12. Heparin-induced thrombocytopaenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e400

19. Volume–outcome relationship for revascularization procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e40120. Medical therapy, secondary prevention, and strategies for follow-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e401

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e401

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c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2e384

1. Preamble

The full-text version of the ESC/EACTS Guidelines on myocar-dial revascularization was adjusted by the Task Force selectedby the Czech Society of Cardiology representing professionalsinvolved in the medical care of patients with this pathology.Class IA means the strongest recommendation based on thelevel of evidence and strength of recommendation, and classIII means the therapy is not recommended and may beharmful.

2. Introduction

In 2014, coronary artery bypass grafting (CABG) celebratedthe 50th anniversary of the first procedures performed in1964. Thirteen years later, the first percutaneous coronaryintervention (PCI) was performed and PCI has become one ofthe most frequently performed therapeutic interventions inmedicine.

3. Scores and risk stratification

Myocardial revascularization in the elective setting is appro-priate when the expected benefits, in terms of survival orhealth outcomes (symptoms, functional status, and/or qualityof life), exceed the expected negative consequences of the

Table 1 – Risk models to assess short-term (in-hospita

Score Develop mentcohort

(patients,des ign )

Patientinclusion

Coronaryprocedures

Number ofvariables

Cli nical Anato mi

STS Score n = 774 88 1Multicen tre

01/200 6–

12/200 6100%

(i)CABG 40 2

EuroSCOREII

n =16 82 8Multicen tre

05/201 0–

07/201 0

47%(i)CABG 18 0

ACEF n = 4 55 7Single-cen tre

2001–

2003- 3 0

NCDRCathPCI

181 77 5Multicen tre

01/200 4–

03/200 6100% PCI 8 0

EuroSCORE n =19 03 0Multicen tre

09/199 5–

11/199 5

64%(i)CABG 17 0

ACEF = age, creatinine, ejection fraction; (i)CABG = (isolated) cocular Data Registry; PCI = percutaneous coronary intervention;

aWhichever occurs last.bPermanent stroke, renal failure, prolonged ventilation, deep stercIf creatinine is 2 mg/dL.

procedure. The Heart Team should take into consideration thecoronary artery disease, age, LVEF and comorbidities, patientpreference, and hospital/operator experience.

Numerous models have been developed for risk stratifica-tion. The limitations of the models restrict the ability torecommend one specific risk model (except EuroSCORE II thatshould replace EuroSCORE). It is also important to acknowl-edge that no risk score can accurately predict events in anindividual patient (Tables 1 and 2).

4. Process for decision-making and patientinformation

4.1. Patient information and informed consent

Patient information needs to be unbiased, evidence-based, up-to-date, reliable, accessible, relevant, and consistent with legalrequirements. These recommendations pertain to patients instable condition.

4.2. Multidisciplinary decision-making (Heart Team)

The Heart Team, made up of clinical or non-invasivecardiologists, cardiac surgeons and interventional cardiolo-gists, provides a balanced, multidisciplinary decision-makingprocess. Multidisciplinary decision-making in a Heart Teamcan minimize specialty bias and prevent self-referral frominterfering with optimal patient care (Table 3).

l or 30-day) outcomes.

Outcome Rec omm end ation Vali dationstudies

Calculation

ca l CABG PCI

In-ho spitalor 30-daya

mortali ty,and in-hospital

morbidityb

I B 5–10 htt p:// riskc alc.sts .org

In-ho spitalmortali ty IIa B IIb C >10 www.euroscore.org

/calc.html

In-ho spitalor 30-daya

mortalityIIb C IIb C 5–10

[Age /ejection fraction (%)]

+ 1c

In-ho spitalmortali ty IIb B <5 -

Ope rativemortali ty III B III C >50 www.euroscore.org

/calcold.html

ronary artery bypass grafting; NCDR = National Cardiovas-STS = Society of Thoracic Surgeons.

nal wound infection, re-operation, length of stay, 6 or 14 days.

Table 2 – Risk models to assess medium- to long-term (≥1 year) outcomes.

Score Develop mentcohort

Patientinclusion

Coronaryprocedures

Numberof variables

Outcome Rec omm end ation Vali dationstudies

Calculation

Cli nical Anato mica l CABG PCI

SYNTAX None, expertopinion

none - 011

(3 gene ral,8 per lesion )

MACC E I B I B >50 www.syntaxsc ore.com

SYNTAXII

1 80 0Multicen tre

03/200 5–

04/200 7

50%CAB G,

50% PCI6 12 4-year

mortali ty IIa B IIa B <5 -

ASCERTCAB G


01/200 2–

12/200 7

100%(i)CABG 23 2 Mortality

>2 year s IIa B <5 -

ASCERTPCI


2004–

2007

100%PCI 17 2 Mortality

>1 year IIa B <5 -

LogisticCli nicalSYNTAX

6 50 8Multicen tre

03/200 5–

04-200 7

100%PCI 3 11

1-yearMACE

andmortali ty

IIa B <5 -

ASCERT = American College of Cardiology Foundation–Society of Thoracic Surgeons Database Collaboration (ACCF–STS) onthe comparative effectiveness of revascularization strategies; (i) CABG = (isolated) coronary artery bypass grafting;MACCE = major adverse cardiac and cerebrovascular events; PCI = percutaneous coronary intervention; SYNTAX = synergybetween percutaneous coronary intervention with TAXUS and cardiac surgery.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2 e385

4.3. Timing of revascularization and ad hoc PCI

Patients with stable coronary artery disease (SCAD) sufferingsevere angina (class Canadian Cardiovascular Society (CCS)Class 3 and those with high-risk anatomy should preferablyundergo revascularization (PCI or CABG) within 2 weeks, andall other patients within 6 weeks. Complex pathologies instable patients should in general not be treated ad hoc, butdiscussed by the Heart Team.

5. Strategies for diagnosis: functional testingand imaging

5.1. Non-invasive tests

The risks of exercise, pharmacological stressors, contrastagents, invasive procedures, and cumulative ionizing radiationmust be weighed against the risk of disease or delayeddiagnosis. Ischaemia imaging has been regarded the mostappropriate in patients with intermediate pre-test probability(15–85%).

5.2. Invasive tests

When non-invasive stress imaging is contraindicated, non-diagnostic, or unavailable, the measurement of fractional flowreserve (FFR) or coronary flow reserve is helpful duringdiagnostic coronary angiography.

5.3. Detection of myocardial viability

The differences in performance between the various imagingtechniques are small and experience and availability com-monly determine which technique is used (Table 4).

6. Revascularization for stable coronary arterydisease

The indications for revascularization are persistence ofsymptoms despite medical treatment and/or improvementof prognosis. Revascularization more effectively relievesischaemia and angina, reduces the use of anti-angina drugs,and improves exercise capacity and quality of life, comparedwith medical therapy alone. The extent, location, and severityof coronary artery obstruction are prognostic factors inaddition to ischaemia and left ventricular function. Theevidence basis for revascularization is derived from severalRCTs. The best current revascularization results achieved withPCI are with new-generation drug-eluting stents (DES) and forCABG with maximal use of arterial grafts.

6.1. Revascularization with the use of PCI

The COURAGE trial randomized patients with moderatedisease, no or mild ischaemia and normal LV function, (LMdisease excluded) to PCI with BMS or medical therapy alone. Ata median follow-up of 4.6 years, there were no significantdifferences in death, myocardial infarction and stroke.Freedom from angina was significantly greater in the PCIgroup. The FAME-2 trial was stopped prematurely due to ahighly significant difference in favour of FFR-guided PCI overmedical therapy (a composite of death, MI, and urgentTVR = 4.3% vs. 12.7%, P = 0.001) (Table 5).

6.2. PCI with DES vs. BMS

The major limitation of most of the previous comparisons isthe lack of use of DES offering 50–70% reduction for repeat TVR.New-generation DES compared with early-generation DES

Table 3 – Multidisciplinary decision pathways, patient informed consent, and timing of intervention.

ACS Multivessel SCAD SCAD withad hoc PCIindication

according topredefined HeartTeam protocols

Shock STEMI NSTE-ACS

Multidisciplinarydecision making

Not mandatoryduring the acutephase. Mechanicalcirculatorysupport accordingto Heart Teamprotocol.

Not mandatoryduring the acutephase.

Not mandatoryduring the acutephase. Afterstabilizationrecommended asin stablemultivessel CAD.

Required. Not required.

Informed consent Verbal witnessedinformed consentor family consentif possible withoutdelay.

Verbal witnessedinformed consentmay be sufficientunless writtenconsent is legallyrequired.

Written informedconsent.a

Written informed consent.a Writteninformedconsent.a

Time torevascularization

Emergency: nodelay.

Emergency: nodelay.

Urgency: within24 h if possible andno later than 72 h.

For patients with severesymptoms (CCS 3) andfor those with high-riskanatomy (left main diseaseor equivalent, three-vesseldisease or proximal LAD ordepressed ventricular function),revascularization (PCI or CABG)should be performed withintwo weeks.For all other patients withSCAD, revascularization(PCI or CABG) should beperformed within six weeks.

Ad hoc.

Procedure Proceed withintervention basedon best evidence/availability. Non-culprit lesionstreated accordingto institutionalprotocol or HeartTeam decision.

Proceed withintervention basedon best evidence/availability. Non-culprit lesionstreated accordingto institutionalprotocol or HeartTeam decision.

Proceed withintervention basedon best evidence/availability. Non-culprit lesionstreated accordingto institutionalprotocol or HeartTeam decision.

Plan most appropriateintervention allowing enoughtime from diagnosticcatheterization to intervention.

Proceed withinterventionaccording toinstitutionalprotocoldefined byHeart Team.

ACS = acute coronary syndromes; CABG = coronary artery bypass grafting; CCS = Canadian Cardiovascular Society; LAD = left anteriordescending; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; PCI = percutaneous coronary intervention; SCAD = stablecoronary artery disease; STEMI = ST-segment elevation myocardial infarction.a This may not apply to countries that legally do not ask for written informed consent. ESC and EACTS advocate documentation of patientconsent for all revascularization procedures.

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reduced TVR by 10–20% with improved safety including death,myocardial infarction and stent thrombosis.

6.3. Revascularization with the use of CABG (Table 6)

The superiority of CABG to a strategy of initial medical therapydemonstrated a survival benefit from CABG in patients with LMor three-vessel SCAD, particularly when the proximal LAD wasinvolved. Benefits were greater in those with severe symptoms,early positive exercise tests, and impaired LV function.

6.4. PCI vs. CABG

Proximal LAD: two meta-analyses reported no significantdifference in mortality, myocardial infarction, or stroke.

Increase in recurrent angina and repeat revascularizationwith PCI is today markedly reduced with DES.

Left main disease: PCI provides at least equivalent results toCABG for lower-severity LM lesions at up to five years of follow-up. The SYNTAX trial (705 patients with predominant distal LMdisease) confirmed comparable primary one-year MACCE (CABG13.7% vs. PCI 15.8%; P = 0.44). In the PRECOMBAT trial (patientswith LM disease) the primary end-point was 6.7% in the CABGgroup and 8.7% in the PCI group, the 1-year composite rate ofdeath, MI or stroke was 4.0% for CABG and 3.3% for PCI.

Three-vessel coronary artery disease: an historical meta-analysis reported no difference in mortality between PCI andCABG. SYNTAX randomly assigned 1800 patients with LM and/or three-vessel CAD to either an early-generation paclitaxel-eluting stent or CABG. At 1 year, 12.4% of CABG and 17.8% of PCI

Table 4 – Indications for diagnostic testing in patients with suspected CAD and stable symptoms.

Asymptomatica Symptomatic

Probability of significant diseaseb

Low (<15%) Intermediate (15–85%) High (>85%)

Classc Leveld Classc Leveld Classc Leveld Classc Leveld

Anatomical detection of CADInvasive angiography III A III A IIb A I ACT angiographye,f III B III C IIa A III BFunctional testStress echo III A III A I A III ANuclear imaging III A III A I A III AStress MRI III B III C I A III BPET perfusion III B III C I A III BCombined or hybrid imaging test

III C III C IIa B III B

CAD = coronary artery disease; CT = computed tomography; MRI = magnetic resonance imaging; PET = positron emission tomography.a Screening for silent (asymptomatic) myocardial ischaemia may be considered in selected high-risk patients, such as those with diabetesmellitus.b Pre-test probability of CAD. Low 0–15%; intermediate 15–85%; high >85% as assessed using the criteria based on ESC Guidelines of SCAD.c Class of recommendation.d Level of evidence.e This refers to CT angiography, not calcium scoring.f CT is considered to perform best in the lower range of pre-test probability (15–50%).

Table 6 – Graft patency after CABG.

Graft Patency at1 year

Patency at4–5 years

Patency at≥10 years

Saphenous vein graft 75–95% 65–85% 32–71%Radial artery 92–96% 90% 63–83%Left IMA >95% 90–95% 88–95%Right IMA >95% >90% 65–90%

CABG = coronary artery bypass grafting; IMA = internal mammaryartery.

Table 5 – Indications for revascularization in patients withstable angina or silent ischaemia.

Extent of CAD(anatomical and/or functional)

Classb Levelc

For prognosisLeft main disease with stenosis >50%a I AAny proximal LAD stenosis >50%a I ATwo-vessel or three-vessel disease withstenosis >50%a with impaired LV function(LVEF <40%)a

I A

Large area of ischaemia (>10% LV) I BSingle remaining patent coronary artery withstenosis >50%a

I C

For symptomsAny coronary stenosis >50%a in the presenceof limiting angina or angina equivalent,unresponsive to medical therapy

I A

CAD = coronary artery disease; FFR = fractional flow reserve;LAD = left anterior descending coronary artery; LV = left ventricular.a With documented ischaemia or FFR ≤0.80 for diameter stenosis<90%.b Class of recommendation.c Level of evidence.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2 e387

patients (P = 0.002) reached MACCE. At 5 years, CABG, ascompared with PCI, significantly reduced overall MACCE withrespective rates of 26.9% vs. 37.3% (P = 0.001). In patients withlow SYNTAX score (0–22) rates of MACCE were similar (Table 7).

7. Revascularization in non-ST-segmentelevation acute coronary syndromes

7.1. Early invasive vs. conservative strategy

All results supported a routine early invasive strategy withsignificantly lower incidence of death, MI or rehospitalization.The benefit was carried mainly in high-risk patients.

7.2. Timing of angiography and intervention

Patients at highest risk (refractory angina, severe heart failure,cardiogenic shock, life-threatening ventricular arrhythmias, orhaemodynamic instability) should undergo an immediate(<2 h) invasive evaluation (Tables 8 and 9). The TIMACS trialrevealed 38% lower incidence of death, myocardial infarction, orstroke at 6 months in high-risk patients with an early (≤24 h) vs.delayed (≥36 h) strategy. In the ACUITY trial a delay of more than24 h before PCI was an independent predictor of mortality.

7.3. Type of revascularization

There are no specific RCTs comparing PCI with CABG. In one-third of patients, angiography will reveal single-vessel disease,allowing ad hoc PCI in most cases. The rate of PCI vs. CABG inmultivessel disease is 80% vs. 20%. Culprit-lesion PCI is the firstchoice. The strategy of multivessel PCI has not been tested;however, incomplete revascularization is associated withmore 1-year MACCE.

Table 7 – Recommendation for the type of revascularization (CABG or PCI) in patients with SCAD with suitable coronaryanatomy for both procedures and low predicted surgical mortality.

Recommendations according to extent of CAD CABG PCI

Classa Levelb Classa Levelb

One or two-vessel disease without proximal LAD stenosis. IIb C I COne-vessel disease with proximal LAD stenosis. I A I ATwo-vessel disease with proximal LAD stenosis. I B I CLeft main disease with a SYNTAX score ≤22. I B I BLeft main disease with a SYNTAX score 23–32. I B IIa BLeft main disease with a SYNTAX score >32. I B III BThree-vessel disease with a SYNTAX score ≤22. I A I BThree-vessel disease with a SYNTAX score 23–32. I A III BThree-vessel disease with a SYNTAX score >32. I A III B

CABG = coronary artery bypass grafting; LAD = left anterior descending coronary artery; PCI = percutaneous coronary intervention;SCAD = stable coronary artery disease.a Class of recommendation.b Level of evidence.

Table 8 – Criteria for high risk with indication for invasivemanagement.

Primary criteria1. Relevant rise or fall in troponin2. Dynamic ST- or T-wave changes (symptomatic or silent)3. GRACE score >140

Secondary criteria4. Diabetes mellitus5. Renal insufficiency (eGFR <60 mL/min/1.73 m2)6. Reduced LV function (ejection fraction <40%)7. Early post-infarction angina8. Recent PCI9. Prior CABG10. Intermediate to high GRACE risk score(http://www.gracescore.org)

CABG = coronary artery bypass grafting; eGFR = estimated glomeru-lar filtration rate; GRACE = Global Registry of Acute Coronary Events;LV = left ventricular; PCI = percutaneous coronary intervention.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2e388

7.3.1. CABGThe general consensus is to wait 48–72 h after culprit-lesionPCI and residual severe CAD. Patients with LM or 3VD involvingthe proximal LAD should undergo surgery during hospital stay.

Table 9 – Recommendations for invasive evaluation and revas

Recommendations

Urgent coronary angiography (<2 h) is recommended in patients at veryassociated heart failure, cardiogenic shock, life-threatening ventricular

An early invasive strategy (<24 h) is recommended in patients with at leAn invasive strategy (<72 h after first presentation) is indicated in patienor recurrent symptoms.

Non-invasive documentation of inducible ischaemia is recommended inbefore deciding on invasive evaluation.

It is recommended to base the revascularization strategy (ad hoc culprit-lstatus and comorbidities as well as the disease severity, i.e. distributioSYNTAX score), according to the local Heart Team protocol.

New-generation DES are indicated for percutanous treatment of significa

ACS = acute coronary syndromes; CABG = coronary bypass graft surgery; Dcoronary syndrome; PCI = percutaneous coronary intervention; SYNTAX =a Class of recommendation.b Level of evidence.

When there is continuing or recurrent ischaemia, ventriculararrhythmias, or haemodynamic instability, CABG should beperformed immediately.

7.3.2. PCINew-generation DES are the default option. Dual antiplatelettherapy should be maintained for 12 months, irrespective ofstent type.

8. Revascularization in ST-segment elevationmyocardial infarction (Fig. 1)

8.1. PCI

Primary PCI is defined as PCI in the setting of STEMI withoutprevious fibrinolysis. The door-to-balloon (DTB) time shouldbe less than 60 min and the infarct-related artery should betreated during the initial intervention. Multivessel PCI duringSTEMI should be considered in patients with cardiogenic shockin the presence of critical stenoses and persistent ischaemia.In the PRAMI trial preventive PCI in non-infarct-relatedcoronary was associated with a reduced risk of death, MI, or

cularization in NSTE-ACS.

Classa Levelb

high ischaemic risk (refractory angina, with arrhythmias, or haemodynamic instability).

I C

ast one primary high-risk criterion (Table 6). I Ats with at least one high-risk criterion (Table 6) I A

low-risk patients without recurrent symptoms I A

esion PCI/multivessel PCI/CABG) on the clinicaln and angiographic lesion characteristics (e.g.

I C

nt coronary lesions in ACS patients. I A

ES = drug-eluting stent; NSTE-ACS = non-ST-segment elevation acute SYNergy between percutaneous coronary intervention with TAXus.

http://www.gracescore.org/

Fig. 1 – Organization of STEMI reperfusion strategies. DI-DO = door-in to door-out time; DTB = door-to-balloon time;EMS = emergency medical service; FMC = first medical contact; FMCTB = first-medical-contact-to-balloon-time;PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2 e389

refractory angina. The radial approach should be preferredwith new-generation DES as default option. Routine use ofthrombus aspiration is not necessary but selective use ofthromboaspiration may improve TIMI 3 flow or prevent stentthrombosis. Patients presenting between 12 and 48 h, evenpain-free, may benefit from PCI. In patients days after the acuteevent only those with recurrent angina or documented residualischaemia/viability may be considered for revascularization.Systematic late PCI of an occluded infarct-related artery instable patients has no incremental benefit (Tables 10 and 11).

8.2. Fibrinolysis

Fibrinolytic therapy is recommended within 12 h of symptomonset in patients without contraindications if primary PCIcannot be performed by an experienced team within 120 min

of FMC, particularly if it can be given pre-hospital and withinthe first 120 min. Facilitated PCI (reduced or normal dosefibrinolysis � GPI followed by coronary angiography/PCI) hasshown no advantage over primary PCI alone. Early, routine,post-thrombolysis angiography with subsequent PCI (3–24 h)reduced the rates of re-infarction and recurrent ischaemia. Incases of failed fibrinolysis or re-infarction the patient shouldundergo rescue PCI.

8.3. CABG

CABG may be indicated in STEMI patients with unsuitableanatomy for PCI who have a patent infarct-related artery, inpatients with cardiogenic shock if the coronary anatomy is notamenable to PCI or for patients with mechanical complica-tions.

Table 10 – Primary PCI for myocardial reperfusion in STEMI: indications and logistics.

Recommendations Classa Levelb

IndicationReperfusion therapy is indicated in all patients with time from symptom onset <12 h duration and persistent STsegment elevation or (presumed) new LBBB.

I A

Primary PCI is the recommended reperfusion therapy over fibrinolysis if performed by an experienced team in a timelyfashion.

I A

In patients with time from symptom onset >12 h, primary PCI is indicated in the presence of continuing ischaemia,life-threatening arrhythmias or if pain and ECG changes have been stuttering.

I C

Primary PCI is indicated for patients with severe acute heart failure or cardiogenic shock due to STEMI independent fromtime delay of symptom onset.

I B

Reperfusion therapy with primary PCI should be considered in patients presenting late (12–48 h) after symptom onset. IIa BLogisticsIt is recommended that the pre-hospital management of STEMI patients be based on regional networks designed todeliver reperfusion therapy timely and effectively, and to offer primary PCI to as many patients as possible.

I B

It is recommended that all EMSs, emergency departments, coronary care units, and catheterization laboratories have awritten updated STEMI management protocol, preferably shared within geographic networks.

I C

It is recommended that primary PCI-capable centres deliver a 24-h/7-day service and ensure for primary PCI to beperformed as fast as possible and at the latest within 60 min of hospital arrival.

I B

Patients transferred to a PCI-capable centre for primary PCI should bypass the emergency department and be transferreddirectly to the catheterization laboratory.

IIa B

ECG = electrocardiogram; EMS = emergency medical service; LBBB = left bundle branch block; PCI = percutaneous coronary intervention;STEMI = ST-segment elevation myocardial infarction.a Class of recommendation.b Level of evidence.

Table 11 – Primary PCI for myocardial reperfusion in STEMI: procedural aspects (strategy and technique).


StrategyPrimary PCI should be limited to the culprit vessel with the exception of cardiogenic shock and persistent ischaemia afterPCI of the supposed culprit lesion.

IIa B

Staged revascularization of non-culprit lesions should be considered in STEMI patients with multivessel disease in caseof symptoms or ischaemia within days to weeks after primary PCI.

IIa B

Immediate revascularization of significant non-culprit lesions during the same procedure as primary PCI of the culpritvessel may be considered in selected patients.

IIb B

In patients with continuing ischaemia and in whom PCI of the infarct-related artery cannot be performed, CABG shouldbe considered.

IIa C

TechniqueStenting is recommended (over balloon angioplasty) for primary PCI. I ANew-generation DES are recommended over BMS in primary PCI. I ARadial access should be preferred over femoral access if performed by an experienced radial operator. IIa AThrombus aspiration may be considered in selected patients. IIb A

BMS = bare-metal stent; CABG = coronary artery bypass grafting; DES = drug-eluting stent; PCI = percutaneous coronary intervention;STEMI = ST-segment elevation myocardial infarction.a Class of recommendation.b Level of evidence.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2e390

9. Revascularization in patients with heartfailure and cardiogenic shock

9.1. Chronic heart failure

Revascularization with CABG or PCI is indicated for symptom-atic relief of angina pectoris in patients with heart failure. Inthe STICH trial surgical revascularization reported significant-ly lower all-cause mortality in favour of CABG confirmed in anobservational cohort during follow-up over 10 years. Earlyrevascularization in the setting of hibernating myocardiumwas associated with improved survival, especially whenthe extent of viability exceeded 10% of the myocardium. The

risk–benefit balance for revascularization in patients withoutangina/ischaemia or viable myocardium remains uncertain.Surgical ventricular reconstruction (SVR) may benefit patientswith less-dilated LV and better LVEF, while those with largerLV and poorer LVEF may do worse (Table 12).

9.2. Cardiogenic shock

Acute myocardial infarction accounts for 75% of cardiogenicshock (incidence 6–8%). Emergency revascularization (PCI orCABG) improved long-term survival (SHOCK trial). The use ofIABP had no long-term benefit (IABP-SHOCK II trial). IABPremains an adjunct for patients with mechanical complica-tions as a bridge to surgery. LVAD therapy can be implemented

Table 13 – Specific recommendations for revascularization in patients with diabetes.


In patients presenting with STEMI, primary PCI is recommended over fibrinolysis if it can be performed withinrecommended time limits.

I A

In patients with NSTE-ACS, an early invasive strategy is recommended over non-invasive management. I AIn stable patients with multivessel CAD and/or evidence of ischaemia, revascularization is indicated in order to reducecardiac adverse events.

I B

In patients with stable multivessel CAD and an acceptable surgical risk, CABG is recommended over PCI. I AIn patients with stable multivessel CAD and SYNTAX score ≤ 22, PCI should be considered as alternative to CABG. IIa BNew-generation DES are recommended over BMS. I ABilateral mammary artery grafting should be considered. IIa BIn patients on metformin, renal function should be carefully monitored for 2–3 days after coronary angiography/PCI. I C

BMS = bare-metal stent; CABG = coronary artery bypass grafting; CAD = coronary artery disease; DES = drug-eluting stent; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction.a Class of recommendation.b Level of evidence.

Table 12 – Recommendations on revascularizations in patients with chronic heart failure and systolic LV dysfunction(ejection fraction ≤35%).


CABG is recommended for patients with significant LM stenosis and LM equivalent with proximal stenosis of both LADand LCx arteries.

I C

CABG is recommended for patients with significant LAD artery stenosis and multivessel disease to reduce death andhospitalization for cardiovascular causes.

I B

LV aneurysmectomy during CABG should be considered in patients with a large LV aneurysm, if there is a risk of rupture,large thrombus formation or the aneurysm is the origin of arrhythmias.

IIa C

Myocardial revascularization should be considered in the presence of viable myocardium. IIa BCABG with surgical ventricular restoration may be considered in patients with scarred LAD territory, especially if apostoperative LVESV index <70 mL/m2 can be predictably achieved.

IIb B

PCI may be considered if anatomy is suitable, in the presence of viable myocardium, and surgery is not indicated. IIb C

CABG = coronary artery bypass grafting; LAD = left anterior descending; LCx = left circumflex; LM = left main; LVESV = left ventricular end-systolic volume; PCI = percutaneous coronary intervention; SVR = surgical ventricular reconstruction.a Class of recommendation.b Level of evidence.

c o r e t v a s a 5 7 ( 2 0 1 5 ) e 3 8 1 – e 4 0 2 e391

as a bridge to transplantation, to recovery or as destinationtherapy. Ventricular septal defect is treated by IABP followed byearly surgical repair. Rupture of the free wall, resulting intamponade should be salvaged by prompt pericardial drainageand surgical intervention. Acute mitral regurgitation (rupture ofthe papillary muscle) should be treated by immediate surgery.

10. Revascularization in patients with diabetes

10.1. Evidence for myocardial revascularization

10.1.1. Stable coronary artery diseaseAmong the CABG stratum patients with high-risk angiograph-ic scores, the 5-year risk of death, myocardial infarction orstroke was significantly lower and amplified for those assignedto revascularization, when compared with medical therapy(24.8% vs. 36.8%, respectively; P = 0.005). No outcome differ-ence between PCI and medical therapy was observed.

10.1.2. Acute coronary syndromesMortality in patients with ACS is two to three times increased indiabetic patients, compared with non-diabetic. Approximately

20–30% of patients with NSTE-ACS have known diabetes,and at least as many have undiagnosed diabetes or impairedglucose tolerance. Diabetes presents a secondary indicationfor high risk and for invasive management. Comparedwith non-diabetic patients, diabetics with STEMI presentlater, are more likely to experience haemodynamic instabil-ity and end-organ damage, and have delayed revasculariza-tion.

10.2. Type of myocardial revascularization

Taking currently available evidence (FREEDOM, SYNTAXdiabetic subset, CARDia trials) into consideration, CABG isthe revascularization modality of choice among diabeticpatients with multivessel CAD; however, PCI can be consid-ered as a treatment alternative among diabetic patients withmultivessel disease and low SYNTAX score (≤22). A sensitivityanalysis revealed that the superiority of CABG over early-generation DES for the endpoint MACCE was most pronouncedamong patients with high SYNTAX score, but not significant inthose with low SYNTAX score. All RCTs have shown higherrates of repeat revascularization procedures after PCI com-pared with CABG, in diabetic patients.

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10.3. Revascularization with the use of PCI or CABG

Compared with BMS, all DES showed a rate of TVR that waslower by 37–69%. Superior survival observed with bilateral IMAgrafting has been seen not to depend on diabetic status. Indeed,alternative strategies—including use of the radial artery inpatients with an excessively high risk for sternal complications(e.g. obese patients)—have been shown to be safe.

10.4. Antithrombotic and anti-diabetic medications

There is no indication that antithrombotic pharmacotherapyshould differ. Because of the risk of lactic acidosis in patientsreceiving iodinated contrast media, it is generally stated thatadministration of metformin should be suspended beforeangiography or PCI, and resumed 48 h later, subject toadequate renal function (Table 13).

11. Revascularization in patients with chronickidney disease

Myocardial revascularization in patients with chronic kidneydisease (CKD) is underused. Current treatment strategies arebased on retrospective analyses of RCTs and data from largeregistries.

In patients with moderate chronic kidney disease, CABG isassociated with lower mortality compared with PCI and theoff-pump approach may reduce the risk of perioperative acuterenal failure and/or its progression.

In patients with severe chronic kidney disease and end-stage renal disease or in haemodialysis, CABG was associatedwith lower risks for death and/or myocardial infarction.Candidates for renal transplantation must be screened formyocardial ischaemia and revascularization.

Preventive hydration with isotonic saline should be startedapproximately 12 h before angiography and continued for atleast 24 h (especially if glomerular filtration rate (GFR) is<40 mL/min/1.73 m2). The implementation of high-dosestatin before diagnostic catheterization should be considered(Table 14).

Table 14 – Specific recommendations for patients with modera

Recommendations

CABG should be considered over PCI in patients with multivessel CAD aprofile is acceptable and life expectancy is beyond 1 year.

PCI should be considered over CABG in patients with multivessel CAD aprofile is high or life expectancy is less than 1 year.

It should be considered to delay CABG after coronary angiography until thsubsided.

Off-pump CABG may be considered rather than on-pump CABG.

New-generation DES are recommended over BMS.

BMS = bare-metal stent; CABG = coronary artery bypass grafting; CAD =eluting stent; PCI = percutaneous coronary intervention.a Class of recommendation.b Level of evidence.

12. Revascularization in patients requiringvalve interventions

12.1. Primary indication for valve interventions

Overall, 40% of patients with valvular heart disease will haveconcomitant CAD. Coronary angiography is recommended inall men >40 years and post-menopausal women. In patientswith severe comorbidities, the Heart Team may opt fortranscatheter valve interventions (TAVI) (Table 15).

12.2. Primary indication for coronary revascularization

Adding mitral valve repair to CABG in patients with LVdysfunction (LVEF ≤35%) and moderate-to-severe mitralregurgitation offers better survival than CABG alone. Likewise,in patients undergoing CABG, aortic valves with moderatestenosis should be replaced.

13. Associated carotid/peripheral arterydisease

13.1. Associated coronary and carotid artery disease

Up to 40% of patients undergoing carotid endarterectomy(CEA) have significant CAD. CABG carries a greater periproce-dural risk of stroke compared to PCI, the long-term risk persistswith both treatments. Risk factors for all strokes were age,smaller body surface area, emergency surgery, previousstroke, preoperative atrial fibrillation (AF), and on-pump CABGwith hypothermic circulatory arrest. Statins in combinationwith beta-blockers have shown a protective effect. In patientswith previous TIA or stroke and the presence of carotid arterystenosis (50–99% in men; 70–99% in women), CEA performed byexperienced teams may reduce the risk of perioperative strokeor death. The choice of CEA vs. carotid artery stenting (CAS)should be based on patient comorbidities, supra-aortic vesselanatomy, degree of urgency for CABG and local expertise(Tables 16 and 17).

te or severe CKD.

Classa Levelb

nd symptoms/ischaemia whose surgical risk IIa B

nd symptoms/ischaemia whose surgical risk IIa B

e effect of contrast media on renal function has IIa B

IIb BI B

coronary artery disease; CKD = chronic kidney disease; DES = drug-

Table 16 – Carotid artery screening before CABG.


In patients undergoing CABG, Doppler ultrasound scanning is recommended in patients with a history of stroke/TIA orcarotid bruit.

I C

Doppler ultrasound should be considered in patients with multivessel CAD, PAD, or >70 years of age. IIa CMRI, CT, or digital subtraction angiography may be considered if carotid artery stenosis by ultrasound is >70% andmyocardial revascularization is contemplated.

IIb C

Screening for carotid stenosis is not indicated in patients with unstable CAD requiring emergency CABG with no recentstroke/TIA.

III B

CABG = coronary artery bypass grafting; CAD = coronary artery disease; CT = computed tomography; MRI = magnetic resonance imaging;PAD = peripheral artery disease; TIA = transient ischaemic attack.a Class of recommendation.b Level of evidence.

Table 15 – Recommendations for combined valvular and coronary interventions.


Diagnostic modalitiesCoronary angiography is recommended before valve surgery in patients with severe valvular heart disease and any of thefollowing:� history of CAD� suspected myocardial ischaemia� LV systolic dysfunction� in men aged over 40 years and in post-menopausal women� ≥1 cardiovascular risk factor for CAD.

I C

Coronary angiography is recommended in the evaluation of secondary mitral regurgitation. I CCT angiography should be considered before valve surgery in patients with severe valvular heart disease and lowprobability for CAD or in whom conventional coronary angiography is technically not feasible or of high risk.

IIa C

Primary valve intervention and coronary revascularizationCABG is recommended in patients with a primary indication for aortic/mitral valve surgery and coronary artery diameterstenosis >70% in a major epicardial vessel.

I C

CABG should be considered in patients with a primary indication for aortic/mitral valve surgery and coronary arterydiameter stenosis 50–70% in a major epicardial vessel.

IIa C

PCI should be considered in patients with a primary indication to undergo TAVI and coronary artery diameter stenosis>70% in proximal segments.

IIa C

PCI should be considered in patients with a primary indication to undergo transcatheter mitral valve interventions andcoronary artery diameter stenosis >70% in proximal segments.

IIa C

Primary revascularization and non-coronary interventionMitral valve surgery is indicated in patients with severe mitral regurgitation undergoing CABG, and LVEF >30%. I CMitral valve surgery should be considered in patients with moderate mitral regurgitation undergoing CABG to improvesymptoms.

IIa B

Repair of moderate-to-severe mitral regurgitation should be considered in patients with a primary indication for CABGand LVEF ≤35%.

IIa B

Stress testing should be considered in patients with a primary indication for CABG and moderate mitral regurgitation todetermine the extent of ischaemia and regurgitation.

IIa C

Aortic valve surgery should be considered in patients with a primary indication for CABG and moderate aortic stenosis(defined as valve area 1.0–1.5 cm2 [0.6–0.9 cm2/m2 body surface area] or mean aortic gradient 25–40 mmHg in thepresence of normal flow conditions).

IIa C

CABG = coronary artery bypass grafting; CAD = coronary artery disease; CT = computed tomography; LV = left ventricular; LVEF = leftventricular ejection fraction; PCI = percutaneous coronary intervention; TAVI = transcatheter aortic valve implantation.a Class of recommendation.b Level of evidence.

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13.2. Associated coronary and peripheral arterial disease

Peripheral artery disease (PAD) is an important predictor ofadverse outcome after myocardial revascularization. CABG isassociated with a trend for better survival compared to PCI.Selected high-risk patients may benefit from staged orconcomitant myocardial revascularization, with options vary-ing from a one-stage surgical approach to combined PCI andperipheral endovascular repair or hybrid procedures (Table 18).

14. Repeat revascularization and hybridprocedures

Early graft failure after CABG is reported in up to 12% of grafts,but only 3% are clinically apparent. Emergency PCI may limitthe extent of MI compared with re-do surgery. Ischaemia afterCABG may be due to progression of disease in native vessels orlate graft failure. Re-do CABG has a two- to fourfold increased

Table 17 – Carotid artery revascularization in patients scheduled for CABG.


CEA or CAS should be performed by teams achieving a combined death/stroke rate at 30 days of:<3% in patients without previous neurological symptoms<6% in patients with previous neurological symptoms.

I A

It is recommended to individualize the indication for carotid revascularization after discussion by a multidisciplinaryteam including a neurologist.

I C

The timing of the procedures (synchronous or staged) should be determined by local expertise and clinical presentation,targeting the most symptomatic territory first.

IIa C

In patients with a <6-month history of TIA/strokeCarotid revascularization is recommended for 70–99% carotid stenosis. I CCarotid revascularization may be considered for 50–69% carotid stenosis depending on patient-specific factors andclinical presentation.

IIb C

In patients with no previous TIA/stroke within 6 monthsCarotid revascularization may be considered in men with bilateral 70–99% carotid stenosis or 70–99% carotid stenosisand contralateral occlusion.

IIb C

Carotid revascularization may be considered in men with 70–99% carotid stenosis and ipsilateral previous silent cerebralinfarction.

IIb C

CABG = coronary artery bypass grafting; CAS = carotid artery stenting; CEA = carotid endarterectomy; TIA = transient ischaemic attack.The term carotid artery stenosis refers to a stenosis of the extracranial portion of the internal carotid artery, and the degree of stenosis isaccording to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.a Class of recommendation.b Level of evidence.

Table 18 – Management of patients with associated CAD and PAD.


In patients with ACS, it is recommended to postpone vascular surgery and first treat CAD, except when vascular surgerycannot be delayed due to a life- or limb-threatening condition.

I C

The choice between CABG and PCI should follow the general recommendations for revascularization consideringpatterns of CAD, comorbidities, and clinical presentation.

I C

Prophylactic myocardial revascularization before high-risk vascular surgery may be considered in stable patients if theyhave persistent signs of extensive ischaemia or are at high cardiac risk.c

IIb B

ACS = acute coronary syndrome; CABG = coronary artery bypass grafting; CAD = coronary artery disease; PAD = peripheral artery disease;PCI = percutaneous coronary intervention.a Class of recommendation.b Level of evidence.c High cardiac risk (reported cardiac risk often >5%): (1) aortic and other major vascular surgery; (2) peripheral vascular surgery.

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mortality, PCI is the preferred strategy in patients with patentleft IMA. PCI for SVGs is associated with an increased risk ofdistal coronary embolization and intervention via nativeartery may be preferred.

Most PCI-related complications (dissections, vessel occlu-sion, thrombosis and coronary perforation) are successfullytreated in the cath-lab. Urgent surgery is confined to patientswith a large evolving MI that cannot be salvaged percutane-ously, and to those with iatrogenic cardiac tamponade withfailed pericardiocentesis or recurrent tamponade.

Recurrence of symptoms or ischaemia after PCI is the resultof restenosis, incomplete initial revascularization, or diseaseprogression. Restenosis should be treated by repeat PCI withDES, underexpanded stent should be corrected. In patients withrecurrent episodes of diffuse in-stent restenosis associated withmultivessel disease CABG should be considered. Symptomaticdisease progression after PCI (50% of re-interventions) should bemanaged similar to patients without previous revasculariza-tion. Adequate platelet inhibition is minimizing the risk of stentthrombosis, prasugrel and ticagrelor should be preferred overclopidogrel for at least 12 months after stent thrombosis.

Hybrid myocardial revascularization is combining cardiacsurgery with PCI performed consecutively in a hybrid operat-ing room, or sequentially on separate occasions. Hybridprocedures consisting of IMA to LAD and PCI of otherterritories appear reasonable when PCI of the LAD is not anoption or when a complete revascularization during CABGmight be associated with an increased risk.

15. Arrhythmias

15.1. Ventricular arrhythmias

Revascularization plays an important role in reducing thefrequency of ventricular arrhythmias in normal and reducedLV function. Patients with ischaemic LV dysfunction (LVEF<35%) who are considered for primary preventive ICDimplantation should be evaluated for residual ischaemiaand for potential revascularization targets.

Urgent coronary angiography and revascularization shouldbe part of the management of patients with electrical storm, as

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well as antiarrhythmic drug therapy and/or ablation ofventricular tachycardia.

Approximately 70% of survivors of out-of-hospital cardiacarrest have CAD, with acute vessel occlusion observed in 50%.Thus, early coronary angiography and PCI, if appropriate,should be performed, if no obvious non-cardiac cause of thearrhythmia is present.

15.2. Atrial arrhythmias

New-onset AF in patients undergoing PCI occurs in 2–6% ofprocedures and in one-third of patients undergoing isolatedCABG. Beta-blockers and amiodaron significantly decreasethe risk of AF after CABG. Antithrombotic treatmentin patients with AF occurring during or after PCI/CABGshould follow the guidelines for antithrombotic treatment ofAF that occurs outside the setting of PCI/CABG (Section 17).There are no data on whether prophylactic intraoperativeablation of AF has an impact on the occurrence of post-operative AF.

15.3. Concomitant surgical procedures for atrialfibrillation or stroke treatment

Currently, concomitant surgical LAA obliteration as an adjunctto anticoagulation may be considered to reduce stroke risk inCABG patients with a history of AF, but randomized studies areneeded to further clarify this issue.

16. Procedural aspects of coronary arterybypass grafting

16.1. Surgical procedures

16.1.1. Conduit harvest

16.1.1.1. Saphenous vein harvest. Saphenous vein harvest canbe accomplished using open and endoscopic techniques. Ifperformed 'open', the 'no-touch' SVG harvesting techniquemay reduce graft injury and improve patency.

16.1.1.2. Mammary artery harvesting. Internal mammaryarteries are dissected from the chest wall, either as a pedicleor as an isolated (skeletonized) vessel.

16.1.2. Coronary vesselThe patency of a bypass graft is influenced by the character-istics of the anastomosed vessel, the run-off area, the graftmaterial, its manipulation, and its construction.

16.1.3. Completeness of revascularizationAnatomical definition of complete revascularization meansbypass grafting to all epicardial vessels ≥1.5 mm with adiameter reduction ≥50%.

16.1.4. Construction of central anastomosisIf free conduits (vein grafts, radial artery) are used, additionalcentral anastomosis for arterial inflow into the bypass vesselsis utilized in the majority of cases. In the situation with a

higher atherosclerotic risk profile, grafts are anastomosedend-to-side in a Y- or T-shaped configuration to the IMAs.

16.1.5. Bypass graftsThe long-term benefit of CABG is maximized with the use ofarterial grafts, specifically the IMA. Available grafts include theIMA, radial, and seldom used gastroepiploic arteries.

16.1.6. On-pump and off-pump proceduresFor most patients and surgeons, on-pump CABG provides thebest or equal short- and long-term outcomes.

16.1.7. Minimally invasive proceduresMinimally invasive direct coronary artery bypass may repre-sent an attractive alternative to a sternotomy (Table 19).

16.2. Reporting perioperative outcome

Perioperative reporting of outcome after CABG proceduresshould be done on a risk-adjusted basis.

17. Procedural aspects of percutaneouscoronary intervention

17.1. Percutaneous coronary intervention devices

Balloon angioplasty might be an option in small vessels(<2.0 mm). Fully covered stents can be life-saving in the rareevent of coronary perforation. Early-generation DES potentlyreduced angiographic restenosis and ischaemia driven TVR, butwith concerns for very late stent thrombosis. New-generationDES (thin-strut, metallic platforms, limus-based antiprolifera-tive drugs from durable or biodegradable polymers or polymer-free surface) increased efficacy and safety leading to unrestrict-ed use in patients with CAD including diabetes, multivessel andLM disease, acute myocardial infarction, SVG, restenotic lesions,chronic total occlusions and also in patients who requireanticoagulation or undergo non-cardiac surgery. Bioresorbablestents dissolve over time (several months to 2 years) and mayrestore the vasomotion with late lumen enlargement (confir-mation in large-scale RCTs is required). Drug-coated balloonsmay be an option for DES restenosis or for small vessels.Rotational atherectomy might be required in tight and calcifiedlesions to allow subsequent passage of stents.

17.2. Adjunctive invasive diagnostic tools

Intravascular ultrasound is used for: accurate measurements(plaque burden, plaque composition by ‘‘virtual histology’’),optimizing stent expansion (a threshold of 5.0–5.5 mm2), inpatients with stent failure (malapposition, restenosis, stentthrombosis). In the LM disease IVUS-guided stent implanta-tion improved survival. Optical coherence tomography is moreaccurate than IVUS for assessing neointimal thickness, strutapposition, subtle morphological details (malapposition,thrombus, plaque prolapse, residual dissection, coverage, in-stent restenosis, stent fracture, thrombosis) as well as earlystages of cardiac allograft vasculopathy. Pressure-derivedfractional flow reserve (FFR) validated the cut-off figure of

Table 19 – Procedural aspects of CABG.


It is recommended to perform procedures in a hospital structure and by a team specialized in cardiac surgery, usingwritten protocols.

I B

Endoscopic vein harvesting should be considered to reduce the incidence of leg wound complications. IIa ARoutine skeletonized IMA dissection should be considered. IIa BSkeletonized IMA dissection is recommended in patients with diabetes or when bilateral IMAs are harvested. I BComplete myocardial revascularization is recommended. I BArterial grafting with IMA to the LAD system is recommended. I BBilateral IMA grafting should be considered in patients <70 years of age. IIa BUse of the radial artery is recommended only for target vessels with high-degree stenosis. I BTotal arterial revascularization is recommended in patients with poor vein quality independently of age. I CTotal arterial revascularization should be considered in patients with reasonable life expectancy. IIa BMinimization of aortic manipulation is recommended. I BOff-pump CABG should be considered for subgroups of high-risk patients in high-volume off-pump centres. IIa BOff-pump CABG and/or no-touch on-pump techniques on the ascending aorta are recommended in patients withsignificant atherosclerotic disease of the ascending aorta in order to prevent perioperative stroke.

I B

Minimally invasive CABG should be considered in patients with isolated LAD lesions. IIa CElectrocardiogram-triggered CT scans or epiaortic scanning of the ascending aorta should be considered in patients over70 years of age and/or with signs of extensive generalized atherosclerosis.

IIa C

Routine intraoperative graft flow measurement should be considered. IIa C

CABG = coronary artery bypass grafting; CT = computed tomography; IMA = internal mammary artery; LAD = left anterior descending.a Class of recommendation.b Level of evidence.

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0.80 in borderline lesions and multivessel disease. The FAME IItrial demonstrated that, in patients with SCAD, FFR-guided PCIusing DES resulted in less need for urgent revascularizationthan with medical treatment (Table 20).

17.3. Specific lesion subsets

Drug eluting stents are the default devices for all lesions.Bifurcation anatomy may have dynamic variability during PCI(plaque shift, dissection, side-branch occlusion). Despite avariety of different stenting techniques (T-stenting, V-stent-ing, crush and its modifications, culotte, etc.) stent implanta-tion in the main vessel only, followed by provisional balloonangioplasty with or without stenting of the side branch

Table 20 – Recommendations for the clinical value ofintracoronary diagnostic techniques.


FFR to identify haemodynamically relevantcoronary lesion(s) in stable patients whenevidence of ischaemia is not available.

I A

FFR-guided PCI in patients with multivesseldisease.

IIa B

IVUS in selected patients to optimize stentimplantation.

IIa B

IVUS to assess severity and optimize treatmentof unprotected left main lesions.

IIa B

IVUS or OCT to assess mechanisms of stentfailure.

IIa C

OCT in selected patients to optimize stentimplantation.

IIb C

FFR = fractional flow reserve; IVUS = intravascular ultrasound;OCT = optical coherence tomography; PCI = percutaneous coronaryintervention.a Class of recommendation.b Level of evidence.

(with 'kissing' balloon dilation when two stents are required)seems preferred. Left-main lesions require special attention toadequate sizing and deployment (IVUS). Ostial disease isfibrotic, calcified, and relatively rigid. Aorto-ostial disease isresistant to dilation. Chronic total coronary occlusions (TIMI 0flow and duration of ≥3 months) should be treated in thepresence of symptoms or objective evidence of viability/ischaemia in the territory of the occluded artery. Successfullyrevascularized CTOs confer a long-term survival advantage,better relief of angina and functional status.

18. Antithrombotic treatments

Patients should be instructed not to prematurely discontinueoral antiplatelet therapy after stenting.

18.1. Percutaneous coronary intervention in stablecoronary artery disease

18.1.1. Oral antiplatelet therapyDual antiplatelet therapy includes a 150–300 mg oral loadingdose of acetylsalicylic acid (ASA) (or 80–150 mg i.v.) followed by75–100 mg per os (p.o.) daily plus a clopidogrel 300–600 mgloading dose followed by 75 mg daily. A loading dose of 600 mgor more is recommended in patients scheduled for elective PCIif coronary anatomy is known.

18.1.2. Intravenous antiplatelet therapyRecent trials did not demonstrate additional benefit from GPIIb/IIIa inhibitors after a clopidogrel loading dose of 600 mg.

18.1.3. AnticoagulationEnoxaparin (0.5 mg/kg i.v. bolus) or unfractionated heparin(UFH) with an i.v. bolus of 70–100 U/kg remains the standardanticoagulant treatment for elective PCI. Bivalirudin might be

Table 21 – Recommendations for antithrombotic treatment in SCAD patients undergoing PCI.

Recommendations for PCI Classa Levelb

Pretreatment with antiplatelet therapyTreatment with 600 mg clopidogrel is recommended in elective PCI patients once anatomy is known and decision toproceed with PCI preferably 2 h or more before the procedure.

I A

Pretreatment with clopidogrel may be considered in patients with high probability for significant CAD. IIb CIn patients on a maintenance dose of 75 mg clopidogrel, a new loading dose of 600 mg or more may be considered oncethe indication for PCI is confirmed.

IIb C

Antiplatelet therapy during PCIASA is indicated before elective stenting. I BASA oral loading dose of 150–300 mg (or 80–150 mg i.v.) is recommended if not pre-treated. I CClopidogrel (600 mg loading dose or more, 75 mg daily maintenance dose) is recommended for elective stenting. I AGP IIb/IIIa antagonists should be considered only for bail-out. IIa CAntiplatelet therapy after stentingDAPT is indicated for at least 1 month after BMS implantation. I ADAPT is indicated for 6 months after DES implantation. I BShorter DAPT duration (<6 months) may be considered after DES implantation in patients at high bleeding risk. IIb ALife-long single antiplatelet therapy, usually ASA, is recommended. I AInstruction of patients about the importance of complying with antiplatelet therapy is recommended. I CDAPT may be used for more than 6 months in patients at high ischaemic risk and low bleeding risk. IIb CAnticoagulant therapyUnfractionated heparin 70–100 U/kg. I BBivalirudin (0.75 mg/kg bolus, followed by 1.75 mg/kg/h for up to 4 h after the procedure) in case of heparin-inducedthrombocytopaenia.

I C

Bivalirudin (0.75 mg/kg bolus, followed by 1.75 mg/kg/h during the procedure) in patients at high bleeding risk. IIa AEnoxaparin i.v. 0.5 mg/kg. IIa B

ASA = acetylsalicylic acid; BMS = bare-metal stent; CAD = coronary artery disease; DAPT = dual antiplatelet therapy; DES = drug-eluting stent; GP =glycoprotein; i.v. = intravenous; PAD = peripheral artery disease; PCI = percutaneous coronary intervention; SCAD = stable coronary artery disease.a Class of recommendation.b Level of evidence.

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considered for use in patients at high risk for bleeding(Table 21).

18.2. Non-ST-segment elevation acute coronarysyndrome

18.2.1. Oral antiplatelet therapyDual antiplatelet therapy includes ASA with an oral loadingdose of 150–300 mg (or 80–150 mg i.v.), followed by 75–100 mgp.o. daily, and a P2Y12-receptor antagonist.

18.2.1.1. Prasugrel and ticagrelor. Prasugrel (60 mg loadingand 10 mg daily maintenance dose) is a prodrug thatirreversibly blocks the P2Y12 platelet receptor. Based on theTRITON-TIMI 38 trial, in diabetic patients and patients withouthigher bleeding risk, prasugrel is more effective and as safe asclopidogrel. Prasugrel should be considered in patients whopresent with stent thrombosis but is contraindicated inpatients with prior stroke or TIA and generally not recom-mended for patients of ≥75 years of age.

Ticagrelor [180 mg loading dose; 90 mg b.i.d. (twice daily)daily maintenance dose] is a reversibly binding P2Y12inhibitor with a plasma half-life of approximately 6–12 h. Inthe PLATO Trial, ticagrelor was superior to clopidogrel in thecomposite ischaemic endpoint (HR 0.84) and mortality (HR0.79). The rate of TIMI major non-CABG-related bleeding washigher (HR 1.25).

18.2.1.2. Clopidogrel. Clopidogrel is a prodrug leading to anirreversible blockade of the P2Y12 receptor. Based on theCURRENT-OASIS 7 findings, 600 mg loading dose and 150 mg

maintenance dose in the first week may be considered onlywhen prasugrel and ticagrelor are not available or if they arecontraindicated.

18.2.2. Intravenous antiplatelet therapyOverall, no evidence for an additional benefit of routineupstream use of GP IIb/IIIa inhibitors.

18.2.3. AnticoagulationA general rule is to avoid crossover between antithrombins(with the exception of adding UFH to fondaparinux)—especially between UFH and low-molecular-weight heparin(LMWH), and to discontinue antithrombins after PCI except inspecific situations. Benefit of enoxaparin over UFH in reducingmortality and bleeding complications was recently reported ina meta-analysis (Table 22).

18.3. ST-segment elevation myocardial infarction

Patients undergoing primary PCI should receive a combina-tion of DAPT with ASA and a P2Y12 receptor blocker as earlyas possible before angiography, and a parenteral anticoagu-lant.

18.3.1. Oral antiplatelet therapyAn oral loading dose of ASA 150–300 mg (or i.v. 80–150 mg)followed by 75–100 mg p.o. daily should be given in combinationwith the preferred P2Y12 inhibitors, prasugrel (60 mg p.o.loading dose; 10 mg maintenance dose) or ticagrelor (180 mgp.o. loading dose; 90 mg maintenance dose b.i.d.). Importantly,the more potent agents (prasugrel and ticagrelor) should not be

Table 22 – Recommendations for antithrombotic treatment in patients with NSTE-ACS undergoing PCI.


Antiplatelet therapyASA is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg (or 80–150 mgi.v.), and at a maintenance dose of 75–100 mg daily long-term regardless of treatment strategy.

I A

A P2Y12 inhibitor is recommended in addition to ASA, and maintained over 12 months unless there are contraindicationssuch as excessive risk of bleeding. Options are:

I A

� Prasugrel (60 mg loading dose, 10 mg daily dose) in patients in whom coronary anatomy is known and who are proceedingto PCI if no contraindication.

I B

� Ticagrelor (180 mg loading dose, 90 mg twice daily) for patients at moderate-to-high risk of ischaemic events, regardless ofinitial treatment strategy including those pre-treated with clopidogrel if no contraindication.

I B

� Clopidogrel (600 mg loading dose, 75 mg daily dose), only when prasugrel or ticagrelor are not available or are contraindicated. I BGP IIb/IIIa antagonists should be considered for bail-out situation or thrombotic complications. IIa CPre-treatment with prasugrel in patients in whom coronary anatomy not known, is not recommended. III BPre-treatment with GP IIb/IIIa antagonists in patients in not known, is not recommended. III AAnticoagulant therapyAnticoagulation is recommended for all patients in addition to antiplatelet therapy during PCI. I AThe anticoagulation is selected according to both ischaemic and bleeding risks, and according to the efficacy–safety profile ofthe chosen agent.

I C

Bivalirudin (0.75 mg/kg bolus, followed by 1.75 mg/kg/h for up to 4 h after the procedure) is recommended as alternative toUFH plus GP IIb/IIIa receptor inhibitor during PCI.

I A

UFH is recommended as anticoagulant for PCI if patients cannot receive bivalirudin. I CIn patients on fondaparinux (2.5 mg daily s.c.), a single bolus UFH (85 IU/kg, or 60 IU/kg in the case of concomitant use of GPIIb/IIIa receptor inhibitors) is indicated during PCI.

I B

Enoxaparin should be considered as anticoagulant for PCI in patients pre-treated with subcutaneous enoxaparin. IIa BDiscontinuation of anticoagulation should be considered after an invasive procedure unless otherwise indicated. IIa CCrossover of UFH and LMWH is not recommended. III B

ASA = acetylsalicylic acid; GP = glycoprotein; i.v. = intravenous; LMWH = low-molecular-weight heparin; NSTE-ACS = non-ST-segment eleva-tion acute coronary syndrome; PCI = percutaneous coronary intervention; UFH = unfractionated heparin.a Class of recommendation.b Level of evidence.

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used in patients with prior haemorrhagic stroke or withmoderate-to-severe liver disease. If not available or contra-indicated, clopidogrel 600 mg p.o. should be given instead.

18.3.2. Intravenous antiplatelet therapyIt remains unclear whether the clinical benefit observed in On-TIME-2 (high-dose tirofiban upstream vs. downstream provi-sional) are due to upstream vs. downstream administration ordue to systematic vs. provisional administration. Time fromsymptom onset to study drug in overall negative trial FINESSEtrial (abciximab upstream vs. in-cathlab) was twice as long as inOn-TIME 2. GP IIb/IIIa inhibitors as bail-out therapy appearsreasonable.

18.3.3. AnticoagulationRecent trials comparing bivalirudin with UFH without system-atic use of GPIIb/IIIa antagonists showed similar effectivity anduphold concerns over an excess risk for acute stent thrombosiswith bivalirudin, while differences in major bleeding are small.Enoxaparin [0.5 mg/kg i.v. followed by subcutaneous (s.c.)treatment] was superior to UFH, and fondaparinux is notrecommended (Table 23).

18.4. Points of interest and special conditions

18.4.1. Pre-treatment with P2Y12 inhibitorsClopidogrel pre-loading in NSTE-ACS and STEMI was associ-ated with a significant reduction in major cardiovascularevents. Prasugrel pre-loading in NSTEMI is based on theACCOAST study not recommended. The risk–benefit ratio of

pretreatment using ticagrelor prior to diagnostic coronaryangiography is not known.

18.4.2. Intravenous P2Y12 inhibitorsCangrelor is a direct reversible, short-acting (half-life 3 min)P2Y12 inhibitor that showed lower rates of PCI periproceduralthrombotic complications (OR 0.81) and of stent thrombosis(OR 0.59) with no difference in (GUSTO) major bleedingcompared to LD of clopidogrel.

18.4.3. Anticoagulation after percutaneous coronaryintervention in acute coronary syndrome patientsLow-dose rivaroxaban (2.5 mg twice daily) may be consideredin patients who receive ASA and clopidogrel after ACS,particularly after STEMI. The role of direct oral anticoagulantsin combination with DAPT in secondary prevention of ACS ispromising but requires further study.

18.4.4. Anticoagulation during percutaneous coronaryintervention in patients on oral anticoagulationIn elective PCI, no additional anticoagulation is needed if theinternational normalized ratio (INR) is 2.5. Radial accessshould be the preferred choice. Glycoprotein IIb/IIIa inhibitorsshould generally be avoided.

18.4.5. Antithrombotic therapy after percutaneous coronaryintervention in patients requiring oral anticoagulationTriple therapy, consisting of ASA, clopidogrel, and (N)OACafter PCI, should only be given if a compelling indication existsand should be limited in duration (Table 24).

Table 24 – Recommendations for antithrombotic treatment in patients undergoing PCI who require oral anticoagulation.


In patients with a firm indication for oral anticoagulation (e.g. atrial fibrillation with CHA2DS2-VASc score 2, venousthromboembolism, LV thrombus, or mechanical valve prosthesis), oral anticoagulation is recommended in addition toantiplatelet therapy.

I C

New-generation DES are preferred over BMS among patients requiring oral anticoagulation if bleeding risk is low (HAS-BLED 2). IIa CIn patients with SCAD and atrial fibrillation with CHA2DS2-VASc score 2 at low bleeding risk (HAS-BLED 2), initial tripletherapy of (N)OAC and ASA (75–100 mg/day) and clopidogrel 75 mg/day should be considered for a duration of at least onemonth after BMS or new-generation DES followed by dual therapy with (N)OAC and aspirin 75–100 mg/day or clopidogrel(75 mg/day) continued up to 12 months.

IIa C

DAPT should be considered as alternative to initial triple therapy for patients with SCAD and atrial fibrillation with aCHA2DS2-VASc score ≤1.

IIa C

In patients with ACS and atrial fibrillation at low bleeding risk (HAS-BLED 2), initial triple therapy of (N)OAC and ASA(75–100 mg/day) and clopidogrel 75 mg/day should be considered for a duration of 6 months irrespective of stent typefollowed by (N)OAC and aspirin 75–100 mg/day or clopidogrel (75 mg/day) continued up to 12 months.

IIa C

In patients requiring oral anticoagulation at high bleeding risk (HAS BLED 3), triple therapy of (N)OAC and ASA (75–100 mg/day)and clopidogrel 75 mg/day should be considered for a duration of one month followed by (N)OAC and aspirin 75–100 mg/dayor clopidogrel (75 mg/day) irrespective of clinical setting (SCAD or ACS) and stent type (BMS or new-generation DES).

IIa C

Dual therapy of (N)OAC and clopidogrel 75 mg/day may be considered as an alternative to initial triple therapy in selectedpatients.

IIb B

The use of ticagrelor and prasugrel as part of initial triple therapy is not recommended. III CAnticoagulation therapy after PCI in ACS patientIn selected patients who receive ASA and clopidogrel, low-dose rivaroxaban (2.5 mg twice daily) may be considered in thesetting of PCI for ACS if the patient is at low bleeding risk.

IIb B

Anticoagulation during PCI in patients on oral anticoagulationIt is recommended to use additional parenteral anticoagulation, regardless of the timing of the last dose of (N)OAC. I CPeriprocedural parenteral anticoagulants (bivalirudin, enoxaparin or UFH) should be discontinued immediately after primaryPCI.

IIa C

ACS = acute coronary syndrome; ASA = acetylsalicylic acid; BMS = bare-metal stent; CHA2DS2-VASc = Cardiac failure, Hypertension, Age ≥75[Doubled], Diabetes, Stroke [Doubled]–Vascular disease, Age 65–74 and Sex category [Female]); DAPT = dual antiplatelet therapy; DES = drug-eluting stent; (N)OAC = (non-vitamin K antagonist) oral anticoagulant; HAS-BLED = hypertension, abnormal renal/liver function, stroke,bleeding history or predisposition, labile INR, elderly, drugs/alcohol; INR = international normalized ratio; LV = left ventricular; PCI = percu-taneous coronary intervention; SCAD = stable coronary artery disease; UFH = unfractionated heparin.a Class of recommendation.b Level of evidence.

Table 23 – Recommendations for antithrombotic treatment in patients with STEMI undergoing primary PCI.


Antiplatelet therapyASA is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg(or 80–150 mg i.v.) and at a maintenance dose of 75–100 mg daily long-term regardless of treatment strategy.

I A

A P2Y12 inhibitor is recommended in addition to ASA and maintained over 12 months unless there are contraindicationssuch as excessive risk of bleeding. Options are:

I A

Prasugrel (60 mg loading dose, 10 mg daily dose) if no contraindication. I BTicagrelor (180 mg loading dose, 90 mg twice daily) if no contraindication. I BClopidogrel (600 mg loading dose, 75 mg daily dose), only when prasugrel or ticagrelor are not available or are contraindicated. I BIt is recommended to give P2Y12 inhibitors at the time of first medical contact. I BGP IIb/IIIa inhibitors should be considered for bail-out or evidence of no-reflow or a thrombotic complication. IIa CUpstream use of a GP IIb/IIIa inhibitor (vs. in-lab use) may be considered in high-risk patients undergoing transfer for primaryPCI.

IIb B

AnticoagulantsAnticoagulation is recommended for all patients in addition to antiplatelet therapy during PCI. I AThe anticoagulation is selected according to both ischaemic and bleeding risks, and according to the efficacy–safety profileof the chosen agent.

I C

Unfractionated heparin: 70–100 U/kg i.v. bolus when no GP IIb/IIIa inhibitor is planned; 50–70 U/kg i.v. bolus with GPIIb/IIIainhibitor.

I C

Bivalirudin 0.75 mg/kg i.v. bolus followed by i.v. infusion of 1.75 mg/kg/h for up to 4 h after the procedure. IIa AEnoxaparin i.v. 0.5 mg/kg with or without GP IIb/IIIa inhibitor. IIa B

ASA = acetylsalicylic acid; GP = glycoprotein; i.v. = intravenous; PCI = percutaneous coronary intervention; STEMI = ST-segment elevationmyocardial infarction.a Class of recommendation.b Level of evidence.

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Fig. 2 – Algorithm for pre-operative management of patientsunder dual antiplatelet therapy.

Table 25 – Antithrombotic drugs dose adjustment in patients with CKD.

Recommendations

ASA No dose adjustment.Clopidogrel No dose adjustment.Prasugrel No dose adjustment. No experience with end-stage renal disease/dialysis.Ticagrelor No dose adjustment. No experience with end-stage renal disease/dialysis.Enoxaparin No adjustment needed for i.v. use in particular for PCI. Dose adjustment for subcutaneous injection in patients

with creatinine clearance <30 mL/min: half dose.Unfractionated heparin No adjustment of bolus dose.Fondaparinux Contra-indicated in patients with severe renal impairment (GFR <20 mL/min).Bivalirudin � In patients with moderate renal insufficiency (GFR 30–59 mL/min) a lower initial infusion rate of 1.4 mg/kg/h

should be given.� In patients with severe renal insufficiency (GFR <30 mL/min) bivalirudin should not be used.� No reduction in the bolus dose is needed.

Abciximab No specific recommendation. Careful consideration of bleeding risk.Eptifibatide � In patients with moderate renal insufficiency (GFR ≥30 to <50 mL/min), an i.v. bolus of 180 mg/kg should be

administered, followed by a continuous infusion dose of 1.0 mg/kg/min for the duration of therapy.� In patients with severe renal insufficiency (GFR <30 mL/min) eptifibatide is contra-indicated.

Tirofiban In patients with severe renal insufficiency (GFR <30 mL/min) the infusion dose should be reduced to 50%(0.05 mcg/kg/min).

ASA = acetylsalicylic acid; CKD = chronic kidney disease; GFR = glomerular filtration rate; i.v. = intravenous; o.d. = omni diem (every day); s.c.= subcutaneous; PCI = percutaneous coronary intervention.

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18.4.6. Duration of dual antiplatelet therapy afterpercutaneous coronary interventionIt is recommended that DAPT be administered for at least 1month after BMS implantation in SCAD, for 6 months afternew-generation DES implantation in SCAD, and for up to 1 yearin patients after ACS, irrespective of revascularization strate-gy.

18.4.7. Drug interactions: a clopidogrel-related topicPharmacodynamic studies—but not clinical outcome stud-ies—support the use of newer proton pump inhibitors such aspantoprazole.

18.4.8. Renal dysfunctionPatients with CKD should receive the same first-line treat-ment; thereafter, dose adaptation with respect to kidneyfunction is essential (Table 25). In PLATO study, ticagrelor wasparticularly effective in CKD patients.

18.4.9. Surgery in patients on dual antiplatelet therapy(Fig. 2)It is recommended that elective non-cardiac surgery bedelayed until completion of the full course of recommendedand that surgery be performed without discontinuationof aspirin. In patients with high-to-very-high bleedingrisk, clopidogrel should be discontinued 5 days before,prasugrel 7 days, ticagrelor 5 days. Withdrawal of P2Y12inhibitors is not recommended in high-risk cohorts, suchas those with continuing ischaemia and high-risk anatomy.The substitution of DAPT with LMWH or UFH is ineffective.

18.4.10. Antiplatelet therapy monitoring and genetic testingPlatelet function testing or genetic testing may be consideredin specific high-risk situations (e.g. history of stent thrombo-sis; compliance issue; suspicion of resistance; high bleedingrisk).

18.4.11. Patients with hypersensitivity to acetylsalicylic acidIn patients with ASA hypersensitivity, and in whom ASAtherapy is necessary, a rapid desensitization procedure may beperformed.

18.4.12. Heparin-induced thrombocytopaeniaBivalirudin or argatroban, hirudin, lepirudin, and danaparoidhave to be used.

Table 26 – Long-term medical therapy after myocardial revascularization to improve prognosis and recommendations forlifestyle changes and participation in cardiac rehabilitation programmes.


Coronary artery diseaseStatin therapy with an LDL-C goal <70 mg/dL (<1.8 mmol/L) is indicated to start and continue in all patients with CADafter revascularization, unless contraindicated.

I A

Low-dose ASA (75–100 mg/day) is recommended in all patients with CAD.c I AIn patients who cannot tolerate ASA, clopidogrel is recommended as an alternative. I BACE inhibitors are recommended in all patients with CAD if there is presence of other conditions (e.g. heart failure,hypertension or diabetes). ARBs are an alternative, if ACE inhibitors are not tolerated.

I A

All patients should be advised on lifestyle changes (including smoking cessation, regular physical activity, and a healthydiet).

I A

Participation in a cardiac rehabilitation programme to modify lifestyle habits and increase adherence to treatmentshould be considered for all patients requiring hospitalization or invasive intervention after an acute ischaemic eventor after coronary bypass surgery.

IIa A

Coronary artery disease and hypertensionA systolic blood pressure goal <140 mmHg should be considered in patients with CAD. IIa AA DBP goal of <90 mmHg is recommended in all patients. In patients with diabetes a DBP goal <85 mmHg isrecommended.

I A

Coronary artery disease and type 2 diabetesA target for HbA1c of <7.0% is recommended, which is particularly well established for the prevention of microvasculardisease.

I A

Coronary artery disease and chronic heart failureIt is recommended to start and continue ACE-inhibitors in all patients with heart failure or myocardial infarction withLVEF <40%, unless contraindicated.

I A

ARBs are indicated in patients who are intolerant of ACE inhibitors and have heart failure or myocardial infarction withLVEF <40%.

I A

Beta-blocker therapy is indicated in all patients with heart failure or LV dysfunction, unless contraindicated. I AAldosterone receptor antagonist therapy is indicated in patients with persisting symptoms (NYHA class II–IV) and an EF<35%, despite treatment with an ACE inhibitor (or an ARB) and a beta-blocker.

I A

Ivabradine should be considered to reduce the risk of hospitalization for heart failure in patients in sinus rhythm with anEF <35%, a heart rate >70 b.p.m., and persisting symptoms (NYHA class II–IV) despite treatment with an evidence-based dose of a beta-blocker (or maximum tolerated), ACE inhibitor (or ARB), and a mineralocorticoid receptorantagonist (or ARB).

IIa B

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ASA = acetylsalicylic acid; b.p.m. = beats per minute; CAD = cor-onary artery disease; DBP = diastolic blood pressure; EF = ejection fraction; HbA1c = glycated haemoglobin A1c; LDL-C = low-density lipoproteincholesterol; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PCI = percutaneous coronary intervention.a Class of recommendation.b Level of evidence.c For antithrombotic therapy in addition to ASA after PCI.

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19. Volume–outcome relationship forrevascularization procedures

Surgeons' case volume, as a continuous variable, is inverselyrelated to operative mortality (adjusted OR 1.36). The influenceof the hospital is lower (adjusted OR 1.13). American College ofCardiology Foundation/American Heart Association (ACCF/AHA) guidelines on CABG surgery provide a IIb recommenda-tion that cardiac surgery programmes with less than 125 CABGprocedures annually be affiliated with high-volume tertiarycentres [level of evidence C].

Hospital case volumes of <400 PCIs per year and operatorcase volumes of <75 PCIs per year were associated withimpaired outcomes. The best outcomes are obtained withhigh-volume operators practising in high-volume institutions.In the case of primary PCI, it is recommended that, annually,operators should perform at least 75 elective procedures andideally 11 primary PCI procedures in high-volume institutions.

A special training in interventional cardiology has beenproposed by the European Association for PercutaneousCardiovascular Interventions (EAPCI).

20. Medical therapy, secondary prevention,and strategies for follow-up

Myocardial revascularization must be accompanied by medi-cal therapy and other secondary prevention strategies for riskfactor modification and permanent lifestyle changes (Table 26).

r e f e r e n c e *

[1] 2014 ESC/EACTS Guidelines on myocardial revascularization.The Task Force on Myocardial Revascularization of the

* For all other references see original full text ESC document [1].

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European Society of Cardiology (ESC) and the EuropeanAssociation for Cardio-Thoracic Surgery (EACTS). Developedwith the special contribution of the European Association ofPercutaneous Cardiovascular Interventions (EAPCI).Authors/Task Force members: Stephan Windecker, PhilippeKolh, Fernando Alfonso, Jean-Philippe Collet, Jochen Cremer,Volkmar Falk, Gerasimos Filippatos, Christian Hamm, StuartJ. Head, Peter Jüni, A. Pieter Kappetein, Adnan Kastrati,Juhani Knuuti, Ulf Landmesser, Günther Laufer, Franz-Josef

Neumann, Dimitrios J. Richter, Patrick Schauerte, MiguelSousa Uva, Giulio G. Stefanini, David Paul Taggart, LuciaTorracca, Marco Valgimigli, William Wijns, AdamWitkowski. European Heart Journal 35 (2014) 2541–2619.http://dx.doi.org/10.1093/eurheartj/ehu278; The full textrecommendations for formulating and issuing ESC/EACTSGuidelines can be found on the ESC web site (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx).

http://dx.doi.org/10.1093/eurheartj/ehu278

http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx



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Summary of the ESC/EACTS 2014 Guidelines on myocardial ... · Guidelines Summary of the ESC/EACTS 2014 Guidelines on myocardial revascularization. Prepared by the Czech Society of